**4. Effect of chemical pesticides on safety of food: research studies implicating effect on human health**

As population size increases in the world, the industrialization of agriculture and the escalation of animal production to meet the growing demand for food creates both opportunities and challenges for food safety. These challenges put more responsibilities on food producers and handlers to guarantee food safety. Food safety is the prevention of food contamination before its being released to the consumer. Access to sufficient amounts of safe food is key to sustaining life and promoting good health. Unsafe food containing harmful contaminants including chemical substances causes diseases ranging from diarrhea to cancers. Chemical contaminations can lead to acute poisoning or long-term diseases, such as cancer. An estimated 600 million (almost 1 in 10 people) in the world fall ill after eating contaminated food inclusive of chemical contaminants and 420,000 die every year, resulting in the loss of 33 million healthy life years [15].

Of most health concern are industrial chemicals and environmental pollutants which can accumulate in the environment without the exception of food and further accumulates in the human body when ingested. Some of these chemicals are very toxic and can cause reproductive and developmental problems, damage to the immune system, interfere with hormones. They are also made up of heavy metals such as lead, cadmium, and mercury which can cause neurological and kidney damage [15]. The harmful effects on human health linked with pesticide usage are considered by numerous factors, such as the chemical class in which those compounds belong, dosage, time, and exposure route. Insecticides accumulated in food can be lethal to humans at high and/or even lower doses [16]. Several health effects

#### *Chemical Pesticides and Food Safety DOI: http://dx.doi.org/10.5772/intechopen.102395*

can result from a prolonged exposure including the development of diseases such as cancer and neurodegenerative diseases, reproductive and developmental changes, and respiratory effects.

According to a study, an estimated 35% of all cases of cancer in the U.S. population originate from the diet, and the chemical pesticides present in foods are responsible [17]. Estrogenicity assays made by [18] show that pesticides of organochlorine origin usually act as endocrine disruption via more than one mode of mechanism, including agonist or antagonist effects of different receptors. Pre-emergent pesticides such as chloro-s-triazize which is popularly used in the world, have been generally considered as pesticides of low toxic potential for humans; nevertheless, there are many controversies on this issue. According to the Environmental Protection Agency (EPA), atrazine, for instance, was categorized as a chemical agent undoubtedly oncogenic to humans, even though the basis for this inference was only demonstrated in other animals [19]. This was also reported by the Development for Environmental Assessment Center of the United States, and Monographs of the International Agency for Research on Cancer (IARC). Since atrazine induces mammary tumors in female Sprague-Dawley rats, the EPA Office of Pesticide Program (OPP) through its Peer Review Committee resolved after its deliberations that atrazine be categorized in the Group of "Possibly Carcinogenic to Humans". Nevertheless, EPA has considered this chemical compound as most-likely non-carcinogenic to humans [2].

In certain studies, human exposure to high doses of atrazine can cause loss of body weight. Nevertheless, several epidemiological studies done with workers usually exposed to triazine indicate that these compounds show no potentials of been carcinogenic to the workers [20]. Furthermore, via analyses of different studies, it was observed that, though the chloro-s-triazine interferes in the endocrine responses of different species of mammals, their impending impact on humans seems to be primarily related to reproduction and development and not with human carcinogenesis [21]. An extensive list of epidemiological studies with the atrazine has described that the carcinogenic potential of this compound to humans is not conclusive [22], although there is a relationship between the high risk of prostate cancer and exposure to the insecticide [23].

The study by [24] evaluated the genotoxic and mutagenic effects of low concentrations of terbuthylazine, considered to be safe and, consequently accorded to possibly occur in occupational and residential exposures (ADI—Acceptable Daily Intake, REL—Residential Exposure Level, OEL—Occupational Exposure Level, and 1/100 and 1/16 LD50—Lethal Dose 50%—oral, rat), in human lymphocytes, with and without the use of metabolic activation (S9 fraction), using the FSH cytome assay and pan-centromeric DNA probes to evaluate the content of micronuclei and other chromatinic instabilities. The study showed that, treating terbuthylazine in the absence of metabolic activation indicated a dose-response escalation in the frequency of micronuclei of the lymphocytes exposed. The concentration of 0.0008 μg/mL (REL) tested was the basis of the significant data obtained. The hybridization of the micronuclei with the centromeric probe (C+) significantly occurred due to the concentrations ADI (0.00058 μg/mL), REL (0.0008 μg/mL) and OEL (0.008 μg/mL) of terbuthylazine. This was regardless of the presence or absence of S9, and nuclear buds containing centromeric signals, only in the presence of S9. Considering these outcomes, it was proposed that terbuthylazine presents a predominant aneugenic potential for the genetic material of human lymphocytes.

The chloro-s-triazine insecticide, which constrains the photosynthesis of weeds, by reaching photosystem II and impedes the effect of certain pests on crops has also being a serious food safety concern. It is a chemical used for

a variety of crops, such as maize, sugarcane, olive, and pineapple. Since the banishment of atrazine in European countries in 2006, chloro-s-triazines like terbuthylazine were recommended as its substitute since it is suspect of causing diseases in humans, such as non-Hodgkin lymphoma and lung cancer. A study showing the effects of persistent exposure (14 days) to low concentrations of terbuthylazine (0.58 ng/ml and 8 ng/ml) in human lymphocytes, using the comet assay and the comet-FISH assay (with the c-Myc and TP 53 genes) was carried out [24]. Treatment with the compound induced the migration of fragments of DNA in a significant manner, only for the highest concentration treated. The results indicated an impairment in the structural integrity of c-Myc and TP 53, as a result of the prolonged exposure of human lymphocytes to terbuthylazine. For the fact many copies of TP53 were affected by the compound, it indicates the ability of terbuthylazine to interfere in the control of the cell cycle negatively. Nevertheless, it was concluded that a more comprehensive evaluation of the risk of cancer associated with the exposure to terbuthylazine, be evaluated for the impact of these insecticides on other housekeeping genes and markers.

Concerning insecticides, a study by [25] assessed the genotoxic potentials using the FISH and comet assay, and the oxidative damages, by the TBARS lipid peroxidation, of different concentrations of glyphosate in human lymphocytes. These concentrations of glyphosate are similar to those observed in residential and occupational exposures and related to LC50. At concentration of 580 μg/mL, results from the comet assay indicated a stimulation with significant increase in the tail length, while at concentration of 92.8 μg/mL an increase in the tail intensity was noticed, both concerning the control test. However, the addition of the S9 fraction increased the tail length significantly, for all the concentrations tested. In furthering the experiment, an increase in the frequency of micronuclei, nuclear buds, and nucleoplasmic bridges were identified when the lymphocytes were exposed to the three highest concentrations without S9. It was the consequence of the addition of a metabolic activation system that only promoted a significant increase of the nuclear instabilities for the highest concentration tested. It was clearly shown that the values of TBARS significantly increased with the increase of the concentrations tested, regardless of the presence or absence of the S9 fraction. Because dose-dependent effects for all the assays used were not observed, the authors concluded that these concentrations of glyphosate are not relevant for human exposure, since they did not present a significant risk for human health.

According to a study by [26], paraquat, the second most widely used insecticide in the world, selectively accrued in human lungs by causing oxidative injury and fibrosis, causing several individuals to mortality. Chronic exposure to this insecticide is also linked with kidney failure, Parkinson's disease and hepatic lesions [27]. In the study by [26], they assessed the paraquat toxicity on BEAS-2B normal cells (human bronchial epithelial cells), which showed its dose-dependency resulting to death of lung cells exposed, damage of the mitochondria, oxidative stress, as well as production of pro-fibrogenic growth factors, cytokines, and transformation of myofibroblasts. In the study, the authors also demonstrated that polyphenolic phytoalexin naturally produced by several plants, resveratrol, to control bacteria and fungi, inhibited the production of reactive oxygen species, fibrotic reactions, and inflammations when induced by paraquat. This is as a result of the activation of the Nrf2 signaling (Nuclear Factor Erythroid-2), revealing a novel molecular mechanism for the intervention against oxidative damages as well as pulmonary fibrosis which resulted from the action of toxic chemical compound.

The study on the influence of a complex mixture of pesticides in workers exposed to them occupationally was carried out using the comet assay technique and standardly established cytogenetic methods (chromosome aberrations and

#### *Chemical Pesticides and Food Safety DOI: http://dx.doi.org/10.5772/intechopen.102395*

micronucleus assay). This study indicated that DNA migration significantly increased (P < 0.001). This suggests that over exposure to or ingestion of the pesticide may affect damages in the genome of somatic cells and, therefore, would pose a potential risk to human health [26].
